BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1

<b>Background:</b> Cyclin D1 regulates cyclin-dependent protein kinase activity of the cell cycle, and <i>cyclin D1</i> alternative splicing generates a <i>cyclin D1b</i> isoform, acting as a mediator of aberrant cellular proliferation. As alternative splicing pro...

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Main Authors: Jianguo Feng, Xichao Xu, Xin Fan, Qian Yi, Liling Tang
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/12/2/306
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author Jianguo Feng
Xichao Xu
Xin Fan
Qian Yi
Liling Tang
author_facet Jianguo Feng
Xichao Xu
Xin Fan
Qian Yi
Liling Tang
author_sort Jianguo Feng
collection DOAJ
description <b>Background:</b> Cyclin D1 regulates cyclin-dependent protein kinase activity of the cell cycle, and <i>cyclin D1</i> alternative splicing generates a <i>cyclin D1b</i> isoform, acting as a mediator of aberrant cellular proliferation. As alternative splicing processes are sensitive to mechanical stimuli, whether the alternative splicing of <i>cyclin D1</i> is regulated by mechanical stress and what kinds of factors may act as the regulator of mechano-induced alternative splicing remain unknown. <b>Methods:</b> The alternative splicing of <i>Cyclin D1</i> was examined using reverse transcription polymerase chain reaction (RT-PCR) in osteoblast cell lines and keratinocyte cells loaded by a cyclic stretch. The expression of splicing factors and switching defective/sucrose non-fermenting (SWI/SNF) complex subunits were detected in stretched cells using real-time quantitative PCR (RT-qPCR). The protein interaction was tested by co-immunoprecipitation assay (Co-IP). <b>Results:</b><i>Cyclin D1</i> expression decreased with its splice variant upregulated in stretched cells. Serine/arginine-rich splicing factor 1 (SRSF1) and SWI/SNF complex subunit Brahma-related gene-1-associated factor 57 (BAF57), also named SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1), could respond to mechanical stimuli. Overexpression and knockdown experiments indicated the BAF57/SMARCE1 is probably a critical factor regulating the alternative splicing of cyclin D1. Co-IP showed an interaction between BAF57/SMARCE1 and SRSF1, implying a possible underlying mechanism of the regulator role of BAF57/SMARCE1 in the splicing process of cyclin D1. <b>Conclusions:</b> The splicing factor SRSF1 and BAF57/SMARCE1 are possibly responsible for the mechanical stress-induced alternative splicing of cyclin D1.
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spelling doaj.art-3146c562b4d4456a9d2aae72f60855f82023-12-11T17:52:45ZengMDPI AGGenes2073-44252021-02-0112230610.3390/genes12020306BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1Jianguo Feng0Xichao Xu1Xin Fan2Qian Yi3Liling Tang4Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 401120, ChinaKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 401120, ChinaDepartment of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing 401120, ChinaDepartment of Physiology, College of Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 401120, China<b>Background:</b> Cyclin D1 regulates cyclin-dependent protein kinase activity of the cell cycle, and <i>cyclin D1</i> alternative splicing generates a <i>cyclin D1b</i> isoform, acting as a mediator of aberrant cellular proliferation. As alternative splicing processes are sensitive to mechanical stimuli, whether the alternative splicing of <i>cyclin D1</i> is regulated by mechanical stress and what kinds of factors may act as the regulator of mechano-induced alternative splicing remain unknown. <b>Methods:</b> The alternative splicing of <i>Cyclin D1</i> was examined using reverse transcription polymerase chain reaction (RT-PCR) in osteoblast cell lines and keratinocyte cells loaded by a cyclic stretch. The expression of splicing factors and switching defective/sucrose non-fermenting (SWI/SNF) complex subunits were detected in stretched cells using real-time quantitative PCR (RT-qPCR). The protein interaction was tested by co-immunoprecipitation assay (Co-IP). <b>Results:</b><i>Cyclin D1</i> expression decreased with its splice variant upregulated in stretched cells. Serine/arginine-rich splicing factor 1 (SRSF1) and SWI/SNF complex subunit Brahma-related gene-1-associated factor 57 (BAF57), also named SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1), could respond to mechanical stimuli. Overexpression and knockdown experiments indicated the BAF57/SMARCE1 is probably a critical factor regulating the alternative splicing of cyclin D1. Co-IP showed an interaction between BAF57/SMARCE1 and SRSF1, implying a possible underlying mechanism of the regulator role of BAF57/SMARCE1 in the splicing process of cyclin D1. <b>Conclusions:</b> The splicing factor SRSF1 and BAF57/SMARCE1 are possibly responsible for the mechanical stress-induced alternative splicing of cyclin D1.https://www.mdpi.com/2073-4425/12/2/306alternative splicingBAF57/SMARCE1<i>cyclin D1</i>mechanical strain
spellingShingle Jianguo Feng
Xichao Xu
Xin Fan
Qian Yi
Liling Tang
BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1
Genes
alternative splicing
BAF57/SMARCE1
<i>cyclin D1</i>
mechanical strain
title BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1
title_full BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1
title_fullStr BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1
title_full_unstemmed BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1
title_short BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1
title_sort baf57 smarce1 interacting with splicing factor srsf1 regulates mechanical stress induced alternative splicing of cyclin d1
topic alternative splicing
BAF57/SMARCE1
<i>cyclin D1</i>
mechanical strain
url https://www.mdpi.com/2073-4425/12/2/306
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